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Biomedical subjects

M Burt

Publications and source records attributed to M Burt.

99 records · Page 6Linked to original sources
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Surgical access to tumors of the cervicothoracic junction.

BACKGROUND: Surgical resection of tumors of the cervicothoracic junction is often problematic due to the limitations imposed by the thoracic cage and adjacent neurovascular structures. The majority of surgical approaches to this region have been designed with the intent of providing adequate exposure for vertebrectomy with tumor resection and vertebral column stabilization. These approaches do not provide adequate exposure for a heterogeneous group of tumors which also involve the cervicothoracic junction. We used a combined cervicothoracic surgical approach to determine its efficacy in tumor resection. METHOD: Seventeen patients with a heterogeneous group of malignancies arising in a variety of soft tissues underwent combined cervicothoracic resection. The approach consisted of anterior cervical access, median sternotomy, and anterior thoracotomy. RESULTS: Complete gross tumor resection was accomplished in all 17 patients, 15 of whom had negative microscopic margins. Extensive reconstruction was employed in 6 patients. Three patients received intraoperative brachytherapy implants and 5 patients received external-beam postoperative radiotherapy. Local tumor control was obtained in 12 patients, and 10 patients are currently alive, free of disease (median: 12 months; range: 3-47 months). There was no inadvertent sacrifice of neurovascular structures. The sternoclavicular joint was maintained in all patients. There were 4 major complications, and no perioperative mortality associated with the surgical procedure. CONCLUSION: The combined "trap door" technique provides sufficient exposure for resection of cervicothoracic tumors. Surgery is performed with limited morbidity with the sparing of uninvolved neurovascular structures. The sterno-clavicular joint was maintained in all patients. Preliminary results using this approach for resections of tumors of the cervicothoracic junction are encouraging.

Adolescent↗
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Characterization of local inflammatory response in an isolated lung perfusion model.

BACKGROUND: Current phase I trials of isolated lung perfusion for treatment of pulmonary metastases have an arbitrarily determined length of perfusion. Our objective was to examine the temporal course of the local and distant inflammatory response as a function of the length of perfusion (ischemia) and subsequent reperfusion in an equivalent animal model. METHODS: Sixty male Fischer 344 rats were randomized into four groups (n = 15). Each group underwent left isolated lung perfusion with buffered Hespan for 10, 30, 60, or 90 minutes. Subsequently, two subgroups of five animals within each group were allowed to reperfuse for 1 or 3 hours, respectively. Non-perfused right lung was used as control. At each time point, lung specimens were assayed for TNF-alpha by ELISA and histologic sections were examined. RESULTS: There was no significant difference between the left and right lung tissue levels of TNF-alpha at the termination of the ischemic period. However, on reperfusion, the left lung TNF-alpha levels increased significantly above the ischemia baseline in all groups, with a greater magnitude of rise in the groups with 60 and 90 minutes of preceding ischemia (12,757 +/- 1985 vs. 3524 +/- 494 pg/g, and 16,914 +/- 1657 vs. 6530 +/- 1104 pg/g, respectively; p < 0.05). There was no significant elevation in tissue levels of TNF-alpha in the right lung. Histologic changes consistent with early pulmonary edema were first detected at 12 hours following onset of reperfusion. CONCLUSIONS: Reperfusion following prolonged pulmonary ischemia during isolated lung perfusion results in a significant elevation of local tissue levels of TNF-alpha and may render the perfused lung vulnerable to the adverse effects of the inflammatory cascade.

Animals↗
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Effect of enteral and parenteral nutrition on amino acid levels in cancer patients.

BACKGROUND: The syndrome of cancer cachexia can have a significant impact on response to therapy as well as on survival in cancer patients. Therapies directed at metabolic perturbations in cachectic patients are dependent on nutritional repletion and maintenance of adequate amino acid substrate levels. This study compares the ability of oral feeding, enteral nutrition, and total parenteral nutrition to alter plasma amino acid levels in cancer patients. METHODS: Patients with esophageal cancer were stratified by weight loss. Patients with < 20% weight loss were randomized to continue an ad libitum oral diet (group I) or to receive total parenteral nutrition (group II) for 2 weeks; patients with > 20% weight loss were randomized to receive either enteral nutrition (group III) or total parenteral nutrition (group IV) for 2 weeks. Plasma amino acid levels were measured before the study and again after 2 weeks of nutrition support. RESULTS: Before therapy, there was no difference between the groups in total or essential amino acid levels; however, patients in all groups had significantly lower total amino acid levels compared with those of normal controls. After 2 weeks of treatment, patients in group I and III showed no difference in individual, essential, or total amino acid levels. However, patients in groups II and IV showed significant increases in a number of individual amino acids as well as in essential and total amino acid levels after 2 weeks of TPN. CONCLUSIONS: Patients with esophageal cancer demonstrated significant alterations in amino acid profiles compared with those of normal controls. Total parenteral nutrition was superior to ad libitum oral feeding and jejunostomy feeding in repleting plasma amino acid levels.

Aged↗
PubMedDate not supplied

Early postoperative enteral nutrition improves peripheral protein kinetics in upper gastrointestinal cancer patients undergoing complete resection: a randomized trial.

BACKGROUND: Patients with upper gastrointestinal (GI) tract malignancies are at risk for malnutrition and postoperative morbidity and mortality. We examined the protein kinetic effects of early enteral feeding in this population and compared it with results in patients receiving IV fluid. METHODS: Twenty-nine patients undergoing resection of an upper GI tract malignancy were prospectively randomized to either enteral feeding starting on postoperative day (POD) 1 via a jejunostomy tube (FEED, n = 12) or IV fluid (IVF, n = 17). On POD5, all patients underwent a protein metabolic study using [3H]phenylalanine to determine forearm skeletal muscle (nmol phenylalanine/100 g/min) protein net balance. Free fatty acids (FFA, mEq/dL) and insulin levels (mU/mL) were measured. RESULTS: Protein net balance was significantly less negative in the FEED group compared with the IVF group (-1.4 +/- 0.8 vs -5.0 +/- 1.4, p < .05). Respiratory quotient was significantly increased in patients receiving enteral feeding (0.85 +/- 0.02 vs 0.78 +/- 0.02 FEED vs IVF, p < .05). FFA levels were significantly decreased in the FEED group (0.36 +/- 0.04 vs 0.85 +/- 0.07, p < .05). Insulin levels were significantly elevated in the FEED group (19.8 +/- 4.5 vs 9.3 +/- 0.8, p < .05). Insulin levels correlated with amino acid fluxes. CONCLUSIONS: Postoperative enteral nutrition in upper GI cancer patients results in an improvement in protein kinetic net balance and amino acid flux across peripheral tissue. In addition, insulin levels are elevated, and this elevation correlates with amino fluxes across the forearm. By improving peripheral protein kinetics, early postoperative enteral nutrition may potentially contribute to a decrease in postoperative morbidity and mortality in upper gastrointestinal cancer patients.

Amino Acids↗
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Intestinal permeability after early postoperative enteral nutrition in patients with upper gastrointestinal malignancy.

BACKGROUND: Increased intestinal permeability may lead to sepsis in resected upper gastrointestinal (GI) cancer patients. This study sought to determine whether these patients demonstrated increased intestinal permeability and if early postoperative enteral nutrition would alter this result. METHODS: Nineteen patients undergoing complete resection of upper GI malignancy were randomized into two groups: the nonfed group received IV crystalloid, and the fed group started enteral nutrition by jejunostomy on postoperative day (POD) 1. Six nonoperative volunteers were controls. The lactulose/mannitol test was performed on PODs 1 and 5. Ten grams of lactulose and 5 g of mannitol were given, and urine was collected for 6 hours. RESULTS: All patients (nonfed, 1.895+/-0.34; fed, 0.893+/-0.24) had elevated lactulose/mannitol ratios on POD 1 vs controls (0.262+/-0.1; p < .008 and p = .05). These elevated levels returned toward control levels in both groups by day 5 (nonfed, 0.533+/-0.1, p = .06; fed, 0.606+/-0.12, p = .08). CONCLUSIONS: Major upper GI surgery for malignancy resulted in a significant increase in intestinal permeability on POD 1. With or without enteral nutrition, this measure of intestinal permeability returned to normal on POD 5 in well-nourished patients.

Aged↗
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Aged↗
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Hypoglycemia with glycerol salvage: a role in anti-neoplastic therapy?

UNLABELLED: Most tumors are obligate glucose consumers and severe glucose depletion has anti-neoplastic effects. However, an alternate energy source is necessary to support the host. Since glycerol is utilized by all hypoglycemic sensitive normal tissues but not tumors, glycerol may be an ideal alternate energy source. The effects of glycerol on tumor growth, animal survival during systemic hypoglycemia induced by 3-mercaptopicolinic acid (3-MP, a gluconeogenesis inhibitor), and effects of 3-MP on gluconeogenesis from glycerol were studied. Experiment 1-glycerol effect on tumor cell growth; and glycerokinase activity assay. Methylcholanthrene-induced (MCA) sarcoma cells were plated in either glucose free, glucose or glycerol containing medium. Cell counts and viabilities were recorded daily. Cells in glucose group had normal growth pattern and cell viability, while cell counts and viabilities in control and glycerol groups decreased markedly. F344 rats were injected with MCA-sarcoma cells in the flank. Glycerokinase activities in tumor and host liver were assayed on day 20. Activities were 12.3 +/- 2.8, 148.2 + 17.5 assayed on day 20. Activities were 12.3 +/- 2.8, 148.2 +/- 17.5 mumol/g protein/min in tumor and liver, respectively. Experiment 2-glycerol effect on animal survival during hypoglycemia induced by 3-MP. Following a 48 hour fast, 12 Fischer 344 rats were injected (ip) with 3-MP (200mg/kg) and randomized to saline or glycerol perfusion (100mg/kg/hr) groups. Four of 6 rats in the saline group died of hypoglycemia. All rats in the glycerol group survived, but blood glucose levels were increased as compared to the saline group. Experiment 3-3-MP effect on gluconeogenesis from glycerol as compared to lactate. 5 x 10(6) hepatocytes were incubated in glucose-free HBSS containing glycerol (20mM) or lactate (20mM) in the presence (0.5mM) or absence of 3-MP. Glucose production was assayed every 30 minutes for 2 hrs. Glucose production from glycerol was not significantly inhibited in the presence of 3-MP as compared to lactate. CONCLUSION: Glycerol does not support MCA-sarcoma growth and promotes animal survival during severe systemic hypoglycemia induced by 3-MP. However, glycerol also led to increased gluconeogenesis in this model. The use of hypoglycemic agents with glycerol protection of host tissues warrants further study.

Animals↗
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Regional chemotherapy via pulmonary artery with blood flow occlusion in a solitary tumor nodule model.

This study is to evaluate low dose doxorubicin pulmonary artery perfusion with blood flow occlusion compared to systemic administration in a model of solitary intrapulmonary sarcoma nodule in the rat. Tumor nodule was developed via injection of methylcholanthrene-induced sarcoma into the left lung. Doxorubicin was perfused into the left pulmonary artery at a rate of 50 microliters/min for 2 min with 20 min blood flow blockage in all experiments. Pharmacokinetics, toxicity, treatment efficacy were compared between lung perfusion groups and intravenous groups. Doxorubicin levels in tumor, left lung, right lung, heart and serum were measured. Animal daily weights were recorded and a right pneumonectomy was performed following treatment to assess toxicity and tolerated perfusion dose. Tumors were weighed following treatment to evaluate treatment efficacy. Doxorubicin delivered via pulmonary artery caused a significant higher drug level in tumor tissue and perfused lung with a low drug level in heart, right lung and serum as compared to intravenous administration. Animals in perfusion groups had normal growth pattern and survived after pneumonectomy when a dose of 0.5 mg/kg doxorubicin was perfused. Tumor weight was significantly decreased after treated with 0.5 mg/kg of doxorubicin lung perfusion as compared to same dose of doxorubicin intravenous treatment. Pulmonary artery perfusion with blood flow occlusion may offer an effective lung chemotherapeutic model. 0.5 mg/kg doxorubicin for lung perfusion has acceptable local lung toxicity and no significant systemic toxicity and is pharmacokinetically and therapeutically superior to systemic administration in this solitary intrapulmonary tumor nodule model in the rat.

Animals↗